Molecular, Viral and Clinical Features of Alcohol- and Non-Alcohol-Induced Liver Injury

Round 1

Reviewer 1 Report

Very comprehensive narrative review on alcohol and liver disease. Comments below:

 

1. In abstract and throughout if the authors are referring to SARS-CoV2 as the coronavirus then please refer to this virus.
2. Please review manuscript to improve English grammar: “Additional prevalence of ethnic, genetic, and viral vulnerability is presented.” - “is” should be replaced with “are”.
3. Considering adding the university affiliation for Charles Saul Lieber, in the first sentence.
4. Permission to use Figure 1 obtained ?
5. The following text should be placed in the Figure legend and not in body of text “The figure was retrieved from an open access report …”
6. Consider removing “High” from the following statement: “High concentration of alcohol in the blood, can lead to fetal alcohol syndrome, which can lead to brain damage 326 and impaired growth of the fetus [54].”
7. Please provide the method for common measurement of ethanol in the clinical laboratory as opposed to just listing the following statement: “ In clinical settings, plasma and serum samples are typically used to quantify ethanol or to evaluate liver enzymes.”
8. One center’s experience does not equate standard of care. The following section should be removed or revised to ensure balanced approach: 4.5. Suggested clinical approach

Author Response

Very comprehensive narrative review on alcohol and liver disease. Comments below:

• Thank you for the comment. I will respond to the comments in italics.

In abstract and throughout if the authors are referring to SARS-CoV2 as the coronavirus then please refer to this virus.

• Thank you for the comment, we referred to the virus

Please review manuscript to improve English grammar: “Additional prevalence of ethnic, genetic, and viral vulnerability is presented.” - “is” should be replaced with “are”.

• Thank you for the comment. I wrote "vulnerabilities are".

Considering adding the university affiliation for Charles Saul Lieber, in the first sentence.

•  Professor Lieber, died 16 years ago. During his life he was a faculty member in different Universities in Europe and USA,

Permission to use Figure 1 obtained ? yes

The following text should be placed in the Figure legend and not in body of text “The figure was retrieved from an open access report …”

• Thank you, we appreciate the suggestion.

Consider removing “High” from the following statement: “High concentration of alcohol in the blood, can lead to fetal alcohol syndrome, which can lead to brain damage and impaired growth of the fetus [54].”

• Thank you -we did             

Please provide the method for common measurement of ethanol in the clinical laboratory as opposed to just listing the following statement: “ In clinical settings, plasma and serum samples are typically used to quantify ethanol or to evaluate liver enzymes.”

• We described the methods in agreement with your suggestion 

"One center’s experience does not equate standard of care. The following section should be removed or revised to ensure balanced approach:. 

• yes,we have did.

Reviewer 2 Report

This review article is written by a group of authors discussing the molecular, viral, and clinical features of alcohol and non-alcohol induced liver injury.

 

1. It is suggested to simplify the first Part – it has 4 figures and 2 tables, whereas 1 figure was included for Part 4 and no figures or tables for other parts. The same topic has been comprehensively reviewed elsewhere.
2. Both Part 1 and Part 2 discuss CYP2E1. Therefore, it is suggested to combine the contents.
3. It would be better to include a Conclusion/Discussion.
4. It is suggested to include COVID-19 as it is the main topic of Part 4.
5. On page 7 line 265. What is the meaning of RS?
6. On page 9 line 336-337. Full names of EtG and EtS are suggested to be moved to Page 8 line 332 where they first appeared.

Author Response

1. It is suggested to simplify the first Part – it has 4 figures and 2 tables, whereas 1 figure was included for Part 4 and no figures or tables for other parts. The same topic has been comprehensively reviewed elsewhere.

Thank you for the comment. The topic is continuously discussed and reviewed since the discovery of the MEOS. The present paper reviews the most important concepts.

2. Both Part 1 and Part 2 discuss CYP2E1. Therefore, it is suggested to combine the contents.

Thank you for the comment. The part 1 and part 2 have been combined, please see the revised manuscript.

3. It would be better to include a Conclusion/Discussion.

Thank you for the comment. The conclusions have been included, please see the section 5.

4. It is suggested to include COVID-19 as it is the main topic of Part 4.

Thank you for the comment.  In the present section 3-Coronavirus, I introduced a paragraph about the virus as requested. please see line398-line407. 

5. On page 7 line 265. What is the meaning of RS?

Thank you for the comment. The term RS was changed, please see the line270 (retinoid signals ).

6. On page 9 line 336-337. Full names of EtG and EtS are suggested to be moved to Page 8 line 332 where they first appeared.

Thank you for the comment.  please see the line 333.

Round 2

Reviewer 2 Report

The authors have addressed the comments. 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

The review from Neuman and collegues aims at providing a comprehensive summary of the liver disease associated with alcohol consumption and the link with other relevant disorders.

The way the review is presented is disconnected as it is, it lacks the flow and needs extensive editing in the form and presentation of the data.

in addition, the text needs to be edited since there are typo or grammatical errors.

 

This reviewer suggests to revise the review and make it more fluid.

 

 

Author Response

We appreciate very much your opinion. We made the requested revisions

Reviewer 2 Report

This is not a well-written manuscript, very hard to read.

I think the author did not check their manuscript, for example, even though the CYP2E1 should be cytochrome p450 2E1, not as the author mentioned cytochrome 2E1. This manuscript is not shown fluently writing.

Author Response

We appreciate very much your review.  We made the requested revisions

Reviewer 3 Report

The Authors of the paper aimed to describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver, select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure, provide therapeutic ideas to prevent alcohol-induced liver injury, reflection about rare diseases and alcohol consumption. This manuscript is a significant contribution to the scientific discussion about mechanism and diagnoses of alcoholic and non-alcoholic liver disease.

Text and table editing and minor language revisions should be made. I recommend it for publication after minor revision.

Author Response

We appreciate very much your opinion. We are very lucky t have your scientific opinion. We made the requested revisions.

Reviewer 4 Report

The manuscript (cimb-1532389) entitled "Cellular, molecular, viral, and clinical feature of alcohol and non-alcohol induced liver disease” described enzymes related to alcohol metabolism, especially MEOS in the first section, and the second section provided contents about CYP2E1.Very strangely, the content that should be described in the introduction is described in the third section, and eve more strangely, the content related to COVID-19 and liver disease is described in a very haphazard manner out of context. It doesn’t feel like anyone has read and reviewed it from cover to cover. Each part has enough parts to be helpful to readers, but it did not seem as a scientific paper in its present form. It would be better to reinforce each part and rewrite it as a different paper. Unfortunately, this paper is considered to be inappropriate for publication in Current Issues in Molecular Biology.

Author Response

Dear Reviewer,

The review describes several aspects in several sections of the manuscript. The authors are senior scientists and clinicians that dedicated their life to cure  and to research the diseases described.

The content related to COVID-19 and liver disease is described by an internal medicine specialist in liver disease. His expertise on the subject is enforced by the fact that he is leading a clinic of COVID 19 in one of the largest hospitals.  I apprecie you reading and reviewed the article "from cover to cover"and considering that " Each part has enough parts to be helpful to readers".  We will certainly appreciate your opinion "to reinforce each part and to write an additional review.

Thank you again for the work spent on reviewing the paper.

Round 2

Reviewer 1 Report

The review from Neuman and colleagues has the aim of describing advances in the field of alcohol and non-alcohol induced liver diseases. The manuscript appears not well organized and a bit confusing to this reviewer. It goes from the discovery of specific enzymes to clinical aspects and managing of patients. Despite of interest, the different sections are not well connected. Moreover, COVID19 is a very hot topic nowadays, but it is a different topic that should be considered as separate.

I also suggest to deeply edit the text; some sentences contain more than one verb and are not conclusive.

 

Reviewer 4 Report

As previously reviewed, the paper recommended that the content related to COVID-19 and the content related to alcohol metabolism be described separately, but the content did not any meaningful change.
It is hard to agree with the publication with an incomprehensible composition.